tbuckley/cabot-search huggingface dataset:
Machine learning (ML)-based quantification of tumor-infiltrating lymphocytes (TIL) and clinical outcomes of patients with melanoma treated with immune-checkpoint inhibitors (ICI).
Authors: Elio Adib, Mehrdad Rakaee, Amin Nassar, Elias Bou Farhat, F. Stephen Hodi, David J. Kwiatkowski
Journal: Journal of Clinical Oncology (2023)

9560 Background: TIL quantification has shown promising prognostic and predictive impact in various tumors treated with ICI. More recently, TIL therapy has become an emerging treatment agent for ICI-refractory melanoma. In this work, we studied the effect of intrinsic TILs on clinical outcomes of patients with melanoma treated with ICI and quantified its utility as a biomarker in combination with tumor mutational burden (TMB). Methods: We applied a previously developed ML model to process digital whole-slide images of hematoxylin and eosin slides to quantify TIL density (TIL/mm2) in 182 metastatic melanoma samples treated with ICI at the Dana-Farber Cancer Institute. All samples underwent next-generation targeted-panel sequencing and had available TMB data (mutations/megabase). Overall survival (OS) was calculated from the data of ICI initiation to the date of death. TTF was calculated from the data of ICI initiation to the date of next line treatment or death. Alive patients were censored at the date of last follow-up. Multivariable cox regression was used to estimate adjusted hazard ratios (adj-HR) and p-values (adj-p), with TMB, prior lines of treatment and regimen type (single vs. combination ICI) used as covariates. TMB-high (TMB-H) group was defined as samples with TMB≥10. TIL-high (TIL-H) group was defined as samples with TIL density higher than the median. Results: Of 182 patients, 60% (110/182) were male and the median age at ICI start was 65.5 years. 63% (115/182) of patients received single-agent ICI (anti-PD1 or anti-CTLA4). Of 182 tumor specimens assessed for TILs, 47 (25.8%) were obtained from the primary site. There was no difference in TIL density (medians 583 vs. 817 TILs/mm2, p=0.57; 709 TIL/mm2 for full cohort) or TMB (medians 11.4 vs 12.2 mutations/megabase) between primary and metastatic samples, respectively. Moreover, there was no correlation between TIL density and TMB (pearson’s correlation coefficient = 0.92, p=1) across all samples. Compared to patients in the TIL-low (TIL-L) category, patients in TIL-H had significantly longer median TTF (33.9 [15.9-NR] versus 13.0 [7.8-18.6] months, adj-HR: 0.53 (95% CI: 0.36-0.78); adj-P=0.0012), while there was no difference in OS (P=0.57). In fact, patients in the TMB-H/TIL-H group had the longest TTF, followed by TMB-H/TIL-L, TMB-L/TIL-H then TMB-L/TIL-L (table). Conclusions: Our results support the potential use of ML-based TIL scoring as a novel and independent biomarker to predict time to failure on ICI. There is ongoing effort to validate our findings in an external dataset. [Table: see text]
A phase 1b study of crizotinib in combination with temsirolimus in pediatric ALK- or MET-aberrated relapsed or refractory neuroblastoma (ITCC-053): Results of the phase 1 part.
Authors: Kim Schellekens, Reineke Anna Schoot, Natasha K.A. van Eijkelenburg, Alwin Huitema, Michela Casanova, Dirk Reinhardt, Lynley V. Marshall, Isabelle Aerts, Giuseppe Barone, Louis Chesler, Jennifer Tall, Debbie Hughes, Rana Dandis, Lucas Moreno, Pauline L.H. Winkler-Seinstra, Keith D. Wilner, C Michel Zwaan, Jasper van der Lugt
Journal: Journal of Clinical Oncology (2023)

10036 Background: Preclinical data in neuroblastoma (NBL) models provided evidence that the addition of an mTOR inhibitor with crizotinib may overcome the relative resistance to ALK inhibitors (Berry et al., 2012, Cancer Cell). The primary objective of this phase 1b trial was to establish the recommended phase 2 dose (RP2D) of crizotinib in combination with the mTOR inhibitor temsirolimus in pediatric NBL patients. Methods: Patients aged 1-21 years with relapsed/refractory ALK/MET aberrated NBL were eligible to enroll onto stratum 2 of the CRISP trial (EudraCT: 2015-005437-53, ITCC-053), sponsored by Erasmus MC. This was an open-label, non-randomized, two-stage phase 1b dose finding study. Crizotinib was dose escalated using the EWOC method in four dose levels (DL) ranging from 100 mg/m 2 to 280 mg/m 2 twice daily (BID) in 28 day cycles. Temsirolimus was administered intravenously in a fixed dose of 60 mg/m 2 /week. Both starting doses were reduced compared to the single agent RP2D because of an expected CYP3A4 interaction. Primary endpoint was dose limiting toxicity (DLT) during cycle 1. Radiological disease assessments and blood sampling for pharmacokinetics were scheduled per protocol. Results: Nine NBL patients were enrolled onto stratum 2 between 06-2018 and 12-2022. Eight patients with a median age of 7 years (range: 1-12) received trial treatment. The temsirolimus dose was reduced to 40 mg/m 2 after the first 3 patients based on unexpected toxicity. DLTs occurred in 2/3 patients treated with crizotinib at DL2 (200 mg/m 2 BID); grade 3 elevated ALT (alanine aminotransferase) and grade 3 gastritis (temsirolimus dose; see table). No DLT occurred in 5 patients treated with crizotinib DL1 (150 mg/m 2 BID). Dose re-escalation of crizotinib to DL2 was considered not feasible. The RP2D was established at 150 mg/m 2 BID crizotinib with 40 mg/m 2 temsirolimus. Frequent grade 3 treatment-related adverse events were anorexia, gastritis, oral mucositis (n = 2) and anemia (n = 3). Treatment, toxicity and response are summarized in table. Conclusions: We established a RP2D of 150 mg/m2 BID crizotinib in combination with 40 mg/m2 temsirolimus. The expansion cohort is currently open for enrollment. Clinical trial information: EUCTR2015-005437-53 . [Table: see text]
Intervening factors for participation and non-participation in colorectal cancer screening in Spain.
Authors: Maria Luz Amador
Journal: Journal of Clinical Oncology (2023)

e22552 Background: The Spanish Ministry of Health introduced a population-based colorectal screening program within its common services portfolio in 2014. The program targeted adults from 50 to 69 years. They receive a personal invitation letter asking them to perform the fecal occult blood test (FOBT). To achieve public health benefits on incidence, mortality and cost-effectiveness from this screening program a 65% participation in the program is needed 1 .Although participation rates have been improved since 2014, there is still room from improvement as only 56% of the Spanish regions reach the participacion threshold 2 . In this study we examined attitudinal and social factors impacting on participation in the target population. Methods: A CAWI survey was conducted among the target population of the screening program using a nation-wide citizen panel. A representative sample of the Spanish population, with size of 5131 valid responses, was obtained. The fieldwork was conducted in June 22 nd . The data was analyzed using a descriptive analysis for the entire sample as well as the logistic regression technique using the maximum likelihood estimation. This technique allows us to determine the variables that have the greatest predictive capacity with respect to the participation (or non-participation) on the (FOBT). Results: We found that 97.6% of people have heard of colon cancer, 86.8% are aware of the test, 72.5% have received the program information letter and 62.5% have performed the test (FOBT). Furthermore, logistic regression demonstrates that the reception of a program information letter (OR=7,381, p&lt;0.01), and the prior knowledge of the screening test (FOBT) (OR=6,768, p&lt;0,01) significantly predicted the participation. Other variables with a high contribution were age between 62-69 (OR= 1,470, p&lt;0.01), the frequency of routine medical check-ups (OR= 1,717, p&lt;0.01), a positive perception of routine medical checkups (OR= 1,659, p&lt;0.01), and personal risk of colon cancer perception (OR= 1,404, p&lt;0.01). Conclusions: The effective participation in the program is influenced by factors that are unrelated to the implementation process (including the reception of the invitation letter). Most influential factors on actual participation on the program are the prior knowledge of the program and the importance attributed to routine heath checkups. Specific interventions on these variables should be done concurrently with expanding coverage in order to achieve the goals of higher effective participation. References: 1. Segnan N, Patnick J, von Karsa L. European guidelines for quality assurance in colorectal cancer screening and diagnosis. Office for Official Publications of the European Communities, 2010. 2. Molina-Barceló A, Moreno Salas J, Peiró-Pérez R, Arroyo G, Ibáñez Cabanell. REC. Desigualdades de acceso a los programas de cribado del cáncer en España y cómo reducirlas. Rev Esp Salud Pública. 2021; 95.
Patient access to precision medicine: Correlation of immune checkpoint inhibitor (ICI) usage in non-small cell lung cancer (NSCLC) with patient household income levels across multiple Asian markets.
Authors: Pieter De Richter, Mei Yee Koo
Journal: Journal of Clinical Oncology (2023)

e18629 Background: 1 st line (1L) advanced/metastatic NSCLC patients wild-type (WT) for EGFR, ALK and ROS1 have been shown to benefit from treatment with ICIs, and these drugs have been incorporated into most treatment guidelines for this cancer. However, some patients cannot afford these costly treatment options, especially in countries where reimbursement coverage is partial/absent. This study uses real-world data to explore the correlation between monthly household income levels (MHHI) and ICI shares in Thailand, Indonesia, Vietnam, Taiwan and mainland China. Methods: Ipsos’ Oncology Monitor is a physician-reported syndicated patient record database. 532 cancer-treating physicians (Thailand = 37, Indonesia = 30, Vietnam = 80, Taiwan = 40, China = 345) were screened for specialty, role and caseload and submitted data on 1,134 1L WT stage IIIB/IV NSCLC patients (aggregate) with known MHHI. Data were collected (online + pen &amp; paper) from July ’21 – June ’22. Results: In all 5 countries, a correlation was observed between MHHI and the percentage of WT patients in each cohort receiving an ICI as part of their current 1L therapy. In Thailand and Vietnam, share of ICIs was ≤10% for patients in the study earning &lt; 39,999 THB and &lt; 12,000,001 VND, respectively. This compared to an ICI share of 79% among the most affluent Thai patients ( &gt; 1,000,000 THB) and 35% among the highest-income Vietnamese patients ( &gt; 12,000,000 VND). In Indonesia, all 8 patients prescribed an ICI were in the highest income bracket ( &gt; 10,000,000 IDR). In Taiwan, the correlation was less pronounced, but those earning &lt; 40,000 NTD per household were still least likely to receive an ICI. In China, patients with a MHHI above 10,000 CNY were most likely to be given an ICI. Conclusions: Results from this study suggest that, among this cohort, there is a clear link between patient household income and likelihood to be prescribed an ICI across 5 different Asian markets. While all patients should have access to the most optimal treatment based on their diagnosis and molecular profile, this does not appear to be a reality in the clinical setting, based on data from this real-world evidence study in Asia. More must be done to ensure equal access to all, regardless of country of residence or income. [Table: see text]
Breast cancer in patients with Lynch syndrome: A single institution retrospective analysis.
Authors: Salvatora tindara Miano, Roberto Petrioli, Ignazio Martellucci, Francesco Montagnani, Serenella Civitelli, Guido Francini, Dario Giuffrida, Maria Antonietta Mencarelli, Alessandra Renieri, Angela Prestifilippo, Edoardo Francini
Journal: Journal of Clinical Oncology (2023)

e22549 Background: Lynch syndrome (LS) is associated with an increased risk of several malignancies including gastrointestinal, genitourinary, gynecologic, skin, and brain cancers. However, whether patients with LS have higher risk of developing breast cancer (BC) or not is still controversial and a relevant clinical question. Methods: From the Santa Maria alle Scotte Hospital registry, we retrospectively identified consecutive patients with LS diagnosed by detecting a germline heterozygous pathogenic or likely-pathogenic variant in MLH1, MSH2, MSH6 or PMS2 on molecular genetic testing within April 2016-January 2022. We compared our sample size to Surveillance, Epidemiology, and End Results Program (SEER) of 2017 National Cancer Institute database. Results: Overall, 43 patients with LS were identified. Of those, 11 (25.6%; 95% CI 1.58-26.72%; p &lt; 0.0001) had histologically confirmed BC, 10 (91%) of whom were hormone receptor positive tumors and BC is the only diagnosis of cancer to date. In this 11 patients median age at diagnosis was 54.5 years. 45% of 11 BC LS patients has germinal MSH2 mutation , 45% of 11% are MSH6 mutaded and has a more aggressive breast cancer. Median follow-up was 3 years and 8 months. All patients are still alive and under treatment. Conclusions: Within the limitations of a small sample size and retrospective design, our analysis suggests a significant association between patients with LS and the diagnosis of primary BC. Validation of such findings through prospective clinical studies with larger samples is warranted and would lead to fundamental modifications to LS screening and follow-up international recommendations.
Sun exposure and associated risks: Insight from an international survey with a focus on the organ transplant recipient population.
Authors: Delphine Kerob, Brigitte Dreno, Thierry Passeron, Susana Puig, Cl Goh, Henry Lim, Fatimata Ly, H. Kang, A. Morita, Jorge Ocampo, Sergio Schalka, L. Wei, Caroline Lefloch, Anne-Laure Demessant, Jean Krutmann
Journal: Journal of Clinical Oncology (2023)

e21578 Background: This survey investigates knowledge and behaviors regarding sun exposure among population who have been treated with immunosuppressive anti-graft rejection drugs because of an organ transplantation. Methods: The survey (N = 17,001) was conducted online in 17 countries (5 continents) from 28 September-18 October 2021. Automated selection from the Ipsos online Panel ensured samples of 1,000 individuals in each country fit the quotas method based on gender, age, employment status, and country regions. Data covered demographics, phototype, exposure habits and practices, knowledge and understanding of risks. The current focus in this abstract was defined as individuals who have been treated with immunosuppressive anti-graft rejection drugs because of an organ transplantation. Results: This sub population represents 3% of the general population (n = 434), it comprised 65% men, average age was 39.7 years (SD:14.6) and 57% were of phototype 1-2. 85% were aware of sun-related skin-health issues, a similar awareness among general population (88%). 79% did know that sun protection is useful when the weather is overcast, a better knowledge compared to the general population (61%). Furthermore, 75% did understand the difference between UVA and UVB vs 30% in the general population. But, 69% indicated it was safe to expose themselves without protection when already tanned, a much larger misconception compared to the general population (23%). Only 46% systematically/often use all protections measures during exposure; still a higher practice compared to the general population (12%). And, 63% said they protected from the sun all year round, a better habit compared to the general population (23%). However, during sun exposure, among the 93% who declared using sunscreen, 85% applied sunscreen only once or twice a day, a worse practice compared to the general population (74%). And when already tanned 37% decreased frequency of application and/or used lower protection (44% among general population). 89% regretted not having previously used better protection, a much stronger regret compared to the general population (57%). Conclusions: Although individuals who have been treated with immunosuppressive anti-graft rejection drugs because of an organ transplantation had better knowledge and behavioral attitudes compared to the general population, this survey shows that even a population at high risk of skin cancers and having a regular medical follow-up does not sufficiently perceive the importance of photoprotection in a prevention objective. This leads to discuss the implementation of new information tools with more impact.
Treatment outcomes in patients (pts) with advanced/metastatic non-small cell lung cancer (NSCLC) harboring <i>MET</i> amplification as a secondary oncogenic driver.
Authors: Alex Ryder, Dina Oksen, Emmanuelle Boutmy, Barbara Ellers-Lenz, Christopher Stroh, Niki Karachaliou
Journal: Journal of Clinical Oncology (2023)

e21056 Background: There is limited published evidence on the treatment outcomes of pts with oncogene driven NSCLC who have developed resistance to targeted therapies or novel therapies such as immune checkpoint inhibitors (ICIs) and have MET amplification ( METamp). METamp has been identified as a secondary driver of EGFR TKI resistance. We report here on real-world (rw) outcomes for these pts. Methods: A non-interventional, descriptive cohort study design was applied using ConcertAI electronic medical record data derived from US community oncology centers and linked with ASCO/CancerLinQ data. Eligible pts had stage IIIB–IV NSCLC, and METamp. Study period: Jan 1, 2004 – Oct 31, 2021. Subgroup analyses included 1: pts with oncogene driven NSCLC who received targeted therapy or ICIs after diagnosis of advanced NSCLC, then progressed and had a positive test for METamp, and 2: pts from subgroup 1 who received an EGFR TKI after diagnosis of advanced NSCLC, then progressed and had a positive test for METamp. The presence of METamp after progression on a therapy was hypothesized to indicate METamp as a secondary driver of resistance. Outcomes were analyzed for pts who received a subsequent line of systemic therapy after progression. Results: Of 8,454 pts with lung cancer and minimum 1 molecular test including MET alterations, 164 had METamp (1.9%) and were included in the study cohort. In subgroup 1, 35 pts had METamp detected (21.3%) after disease progression on a targeted therapy or ICIs (EGFR TKI n = 17, ICIs n = 11, other n = 7). Of those pts, 27 received a subsequent systemic therapy after disease progression. The rw overall response rate (ORR) was 18.5% (95% CI: 6.3, 38.1), the median rw progression-free survival (PFS) was 2.2 months (95% CI: 1.6, 4.2) and the median overall survival (OS) from start of the subsequent therapy was 11.3 months (95% CI: 3.4, 21.3). In subgroup 2, 17 pts had METamp detected after disease progression on an EGFR TKI (erlotinib or afatinib n = 13, osimertinib n = 4). Of those pts, 15 received a subsequent systemic therapy after disease progression. The rw-ORR was 13.3% (95% CI: 1.7, 40.5), median rw-PFS was 2.1 months (95% CI: 1.1, 4.6), and median OS from start of the subsequent therapy was 8.5 months (95% CI: 1.7, 15.2). Conclusions: METamp as a secondary driver of resistance is a new target for systemic therapy in pts with EGFR-mutant NSCLC who have developed resistance to EGFR TKIs. Overcoming this resistance using combinations with MET inhibitors is currently under investigation in several clinical trials. The analyses reported here suggests that the treatments available and current standard of care result in poor outcome for pts with METamp, highlighting the high medical unmet need in this population.
Enhancing lung cancer screening through ‘Saved by the Scan’: Lessons from a multipronged public service advertising program.
Authors: Shreyas S Bellur, Ahmad Ozair, Atulya Aman Khosla, Kristen Ordonez, Papsy Mileti, Debbie Ferrera Aguiar, Bianca Hernandez, Stacy Pagan, Chrissy Cohen, Juan Batlle, Mark Dylewski, Manmeet Singh Ahluwalia
Journal: Journal of Clinical Oncology (2023)

10575 Background: Lung cancer screening rates remain low across the US in populations recommended for screening by low-dose CT (LDCT). Screening rates further declined during the COVID-19 pandemic, particularly in high-risk populations including racial and ethnic minorities. The American Lung Association (ALA) launched a nationwide public service advertising (PSA) program called ‘Saved by the Scan’ to enhance lung cancer screening rates, for which Baptist Health South Florida (BHSF) became the first healthcare system partner. The following work describes this major PSA effort in South Florida to enhance lung cancer screening, and the lessons learned thereof. Methods: A multipronged, institutionally-driven public awareness program, in collaboration with ALA, was initiated in 2021 by BHSF, the largest healthcare organization in the region, and was targeted towards South Florida residents. This innovative multimedia effort used traditional communication modalities, including newspapers, billboards, etc., along with digital modalities, including email and social media, to increase lung cancer screening awareness in both English and Spanish in a locally-adapted manner. Key performance indicators (KPIs), reach, and impact of the program were tracked. The most successful components, as per KPIs, were identified. Deidentified data of screening LDCT done at BHSF was reviewed to determine all individuals screened during 2019-2021 and descriptive statistics were calculated. Results: 4619 individuals from South Florida were screened at BHSF from 2019-2021, 1498 were in 2019, 1193 in 2020, and 1928 in 2021. Screening fell by 20.3% in 2020, likely due to the pandemic, and rose by 61.6% in 2021, helped by the program. Overall, a 21.9% increase from pre-COVID screening rates was seen. In 2022, the total reach of traditional media was estimated to be 4,607,273 individuals. Out of 133,554 emails sent, 36,877 (27.2%) were opened, with a click-through rate of 6.4%. Out of 1,768,438 digital impressions, 16,791 (0.9%) had links clicked. The total number of conversions from digital media was estimated to be 337 individuals with 232 (68.9%) from emails and 105 (31.1%) from social media. Conclusions: Lung cancer screening can be successfully boosted through large organizational efforts, particularly those targeted to needs of the local population. Digital media approaches for improving public health have seemingly low conversion rates but their large outreach provides a high impact. Efforts are warranted to enroll more healthcare systems and scale the program nationwide.